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42 Cards in this Set
- Front
- Back
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Is Huntington's Disease hereditary? Does it skip a generation?
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yes; no,it never skips a generation.
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Is HD a common disease?
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No. It has a low prevalence, 4-10/100,000.
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What is HD's mode of inheritance? What characteristic of inheritance does HD exhibit?
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autosomal dominant; anticipation
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What is anticipation?
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a tendency for the condition to have an earlier and earlier onset in subsequent generations.
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Where is the gene expansion located for HD?
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in the Huntingtin gene on chromosome 4
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Does HD have a high degree of penetrance?
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yep
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What is the classic age of onset for HD?
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35-40 years (this can be variable though:2-80 years)
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What is the cardinal manifestation of HD?
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chorea. This interferes with daily life.
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What other psychiatric diseases can accompany HD?(3)
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anxiety, depression, schizophrenia
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Is HD a progressive disease?
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yes, the chorea worsens.
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What are the symptoms/problems exhibited by a patient with HD? (5)
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chorea, dystonia, dysarthria, sub-cortical dementia and sometimes psychiatric disturbances.
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The deletion of the short arm of chromosome 4, the huntingtin gene, results in abnormalities that do NOT resemble HD. It can be hypothesized, therefore, that HD is what kind of mutation?
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a gain of function mutation
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If a patient has juvenile HD, who specifically did they inherit it from?
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from their father. OR from the mother with juvenile HD.
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Is the age of onset related to maternal or paternal inheritance?
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paternal
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By what age will people with the HD mutation manifest the disease.
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80 years old
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What percentage of people express symptoms by age 45?
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50%
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What other disease does juvenile HD resemble? What are the associated symptoms? (5)
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parkinsons; rigidity, tremor, dystonia, dementia and myoclonic epilepsy
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Do patients with juvenile HD live as long as adults with HD?
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no, patients rarely survive into adulthood.
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Is it possible to to perform presymptomatic tesing for HD? If so, what is used and what data is required?
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yes; a G8 probe; it requires DNA samples from other family members.
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What sequence is expanded in the huntingtin gene?
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the CAG trinucleotide on the 5' end of chromosome 4.
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What is the minimum requirement of CAG repeats to manifest HD?
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40 or more repeats
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What is the range of repeats that is termed "indeterminate"? People within this range may develop HD if they live long enough.
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36-39 repeats
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How many repeats do patients with juvenile HD typically have?
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greatly expanded with 60 or more repeats.
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What is the general term that causes many neurodegenerative conditions involving the brain and cause movement disorders?
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Trinucleotide Repeat Disease (TRD)
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Fragile X and myotonic dystrophy are examples of what?
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Non-translated repeat disorders that play a role in gene regulation.
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What is spinobulbar muscular atrophy?
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a translated trinucleotide repeat disease where the gene encodes for an androgen receptor. It is X-linked.
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Is Spinocerebellar ataxia type 1 and 7 a translated TRD or nontranslated?
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Translated TRD
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HD, DRPLA and Machado-Joseph disease are examples of what?
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a translated TRD
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Is the expansion a stable/set number of repeats in each generation?
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no, it is unstable. There is "play' in the number of repeats from generation to generation.
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What process is suspected to play a role in the transmissiblity?
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meiosis (not well-understood)
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In HD patients, is there a gross atrophy of the hemispheres?
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yes
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Even though HD is a disorder of the whole brain, what area can you label as the primary area?
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the caudate
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Is the hippocampus involved in HD?
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yes
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Desribe the location of the caudate in a patient with HD.
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the caudate is fused anteriorly with the putamen and winds around lateral to the lateral ventricles.
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What part of the caudate is affected the earliest? Does it progressively deteriorate?
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the tail of the caudate. Yes.
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What 2 types of neurons are lost in the caudate and the putamen? Are these neurons lost in the same manner for adult and juvenile HD?
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Enkephalinergic (lost first) and Substance P (lost later) neurons. No, both of these neurons are equally lost in juvenile HD.
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What type of neuron are the enkephalinergic and substance P neurons?
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Medium Spiny Neurons
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What circuit is involved with HD?
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the cortical/basal ganglionic/thalamic circuit
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The cerebral cortex projects to the caudate/putamen via what kind of pathway?
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a glutaminergic excitatory pathway.
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Where does the GABAergic inhibitory pathway project to from the caudate/putamen? This is the direct pathway.
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to the Globus Pallidus interna/Substantia Nigra pars reticulata.
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Describe the indirect pathway leaving the caudate/putamen (in the basal ganglia circuitry for HD)
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The enkephalinergic neurons inhibit the globus pallidus externa. This disinhibits the tonic inhibition of the subthalamic nucleus. The subthalamic nucleus can now excite the Globus Pallidus interna/Substantia nigra pars reticulata.
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What type of medium spiny neuron is involved in the direct pathway from the caudate/putamen to the GPi/SNpr complex?
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Substance P containing neurons.
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